Project Summary/Abstract This project is aimed at understanding the neural mechanisms of learning and memory. An extensive literature has documented the role of the hippocampus, retrosplenial cingulate cortex and anterior thalamus in memory functions. Damage to these brain regions is a primary cause of the memory impairments seen in Alzheimer's disease, age-related memory decline, and various human amnesic syndromes and learning disabilities. Abnormalities in these structures have also been implicated in depression, anxiety and schizophrenia. Understanding the function of these systems is crucial for the development of treatment strategies for patients with these conditions. The memory role of the hippocampus has been well documented and, although they have not been studied as extensively, the retrosplenial cortex and anterior thalamus are also known to play a critical role in learning and memory. However, the precise contribution of each of these brain regions to the learning process remains unclear. Recent findings suggest that these closely interconnected structures form a functional circuit which mediates spatial and contextual memory. The proposed experiments are focused on understanding how memory-related information is represented by neurons in the retrosplenial cortex, and how interactions of the retrosplenial cortex, hippocampus and anterior thalamus support memory functions. In order to investigate this, neuronal activity will be recorded in these brain regions as rats perform various spatial and contextual memory tasks. Optogenetic, chemogenetic and neurochemical methods will be used to suppress neuronal activity in various components of this circuit in order to assess their contributions to functioning in the broader memory circuit. By monitoring neuronal responses as subjects learn and the effects of temporary inactivation within the circuit, it will be possible to determine how memory related information is processed and how memory may fail when damage occurs within the circuit.